The incidence of anal squamous cell carcinoma (SCC) has increased, and treatment has shifted from surgery to chemoradiotherapy (CRT), with salvage abdominoperineal resection being reserved for persistent/recurrent cases. This study evaluates the utility of different tumor regression scoring systems in predicting survival in anal SCC patients, using pathologists' observations and digital pathology. Data of cases managed surgically from 2005 to 2019 were collected. Residual tumor was assessed by multiple methods (gross tumor size, largest focus of tumor on hematoxylin and eosin (H&E) slide, average of residual tumor in all submitted H&E slides, Japanese Esophageal Society, Chirieac, Schneider, Hermann, and College of American Pathologists scoring system). Three expert pathologists individually estimated ("eyeballed") the residual tumor percentage based on residual tumor/tumor bed (single representative H&E slide). The QuPath software was used to measure tumor volume on the same slide. The American Joint Committee on Cancer eighth staging and outcome data were retrieved from electronic medical records. The study involved 48 participants, predominantly female (56%), with a median age of 57 years. Most were Caucasian. Human papillomavirus-positive was present in 77% of those assessed (17/22). Initial treatment included CRT, followed by abdominoperineal resection (79%) or pelvic exenteration (21%). Complications (13%), persistent disease (33%), and recurrence (54%) led to surgical interventions. Fifty-one percent had moderately differentiated SCC, whereas 42% were poorly differentiated. Lymphovascular invasion (4 4%), perineural invasion (38%), and lymph node metastasis (13%) were present. Distant metastasis was rare (2%). Median overall survival was 3.2 years. Positive margins (hazard ratio, 4.12; 95% CI, 1.83-9.28) and larger tumor size (hazard ratio, 1.02; 95% CI, 1.01-1.03) were associated with an increased hazard of death. Most residual tumor measurement methods were not significantly associated with overall survival. Interobserver agreement (based on "eyeballing") was moderate (kappa, 0.4). Computational pathology-based residual tumor percentage was the only method significantly associated with outcome, with each 10% increase in the residual tumor percentage corresponding to a 1.23-fold higher hazard death (95% CI, 1.03; 1.46; P 1/4 .024). This study highlights computational pathology's important role in predicting outcomes in anal SCC treated with CRT and surgery. Specifically, the computational assessment of the residual tumor percentage proves to be a strong predictor of overall survival, outperforming other established tumor regression scoring systems methods. (c) 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background: The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation.Methods: With the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic ma-chine perfusion using our institutionally developed perfusion device.Results: Expanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries. Perfusion duration ranged between 1 and 2 hours for the hypothermic oxygenated perfusion phase and between 4 and 9 hours for the normothermic machine perfusion phase. Three livers were judged to be untransplantable during normothermic machine perfusion based on perfusate lactate, bile production, and macro-appearance. One liver was not transplanted because of recipient issue after anesthesia induction and failed reallocation. Thirteen livers were transplanted, including 9 donors after cardiac death livers (donor warm ischemia time 16-25 minutes) and 4 from donors after brain death. All livers had the standardized lactate clearance >60% (perfusate lactate cleared to <4.0 mmol/L) within 3 hours of normothermic machine perfusion. Bile production rate was 0.2 to 10.7 mL/h for donors after brain death livers and 0.3 to 6.1 mL/h for donors after cardiac death livers. After transplantation, 5 cases had early allograft dysfunction (3 donors after cardiac death and 2 donors after brain death livers). No graft failure or patient death has occurred during follow-up time of 6 to 13 months. Two livers developed ischemic cholangiopathy. Compared with our previous normothermic machine perfusion study, the bile duct had fewer inflammatory cells in histology, but the post-transplant outcomes had no difference.Conclusion: Sequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.

Background: The persistent shortage of liver allografts contributes to significant waitlist mortality despite efforts to increase organ donation. Normothermic machine perfusion holds the potential to enhance graft preservation, extend viability, and allow liver function evaluation in organs previously discarded because considered too high-risk for transplant. Methods: Discarded livers from other transplant centers were transplanted after assessment and reconditioning with our institutionally developed normothermic machine perfusion device. We report here our preliminary data. Results: Twenty-one human livers declined for transplantation were enrolled for assessment with normothermic machine perfusion. Six livers (28.5%) were ultimately discarded after normothermic machine perfusion because of insufficient lactate clearance (>4.1 mmol/L after 4 hours), limited bile production (<0.5 mI/h), or moderate macrosteatosis, whereas 15 (71.5%) were considered suitable for transplantation. Normothermic machine perfusion duration was from 3 hours, 49 minutes to 10 hours, 29 minutes without technical problems or adverse events. No intraoperative or major early postoperative complications occurred in all transplanted recipients. No primary nonfunction occurred after transplantation. Seven livers had early allograft dysfunction with fast recovery, and 1 patient developed ischemic cholangiopathy after 4 months treated with biliary stents. All other patients had good liver function with a follow-up time of 8 weeks to 14 months. Conclusion: In total, 71.5% of discarded livers subjected to ex vivo normothermic machine perfusion were successfully transplanted after organ perfusion and assessment using an institutionally built device. This study challenges the current viability criteria reported in the literature and calls for a standardization of viability markers collection, an essential condition for the advancement of the field. (c) 2021 Elsevier Inc. All rights reserved.

The primary aim of this single‐center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)–based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow‐up of 12‐35 months. No device‐related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP‐based preservation solution. Future studies should further investigate the impact of an FFP‐based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation.

Biliary mucinous cystic neoplasms are rare parenchymal neoplasms with a considerable malignant potential. Due to a lack of diagnostic imaging criteria, histopathologic evaluation remains the definitive method of diagnosis. Resection is the treatment of choice. Here, the authors present a case of biliary mucinous neoplasm in a 39-year-old female with the associated radiographic and histopathologic findings.

Rule out infection, especially Clostridium difficile, then order colonoscopy or computed tomography.

It is uncertain whether the outcomes of patients with indeterminate colitis (IC) undergoing ileal pouch-anal anastomosis (IPAA) deteriorate over time. The aim of this study was to determine the long-term pouch function, quality of life, complications, and incidence of Crohn’s disease after IPAA for patients with IC compared to ulcerative colitis (UC).

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.

The continual improvement in outcome with highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection and visceral transplantation for gut failure stimulated our interest in lifting HIV infection as a contraindication for intestinal and multivisceral transplantation. This report is the first to describe visceral transplantation in a patient with HIV infection. A HAART regimen was introduced in the setting of short-gut syndrome with successful suppression of HIV viral load. The indication for en bloc multivisceral and kidney transplantation was end-stage liver failure with portomesenteric venous thrombosis and chronic renal insufficiency. The underlying hepatic pathology was alcoholic and home parenteral nutrition-associated cirrhosis. Surgery was complicated due to technical difficulties with excessive blood loss and long operative time. The complex posttransplant course included multiple exploratory laparotomies due to serious intra-abdominal and systemic infections. Heavy immunosuppression was required to treat recurrent episodes of severe allograft rejection. Posttransplant oral HAART successfully sustained undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months posttransplant. With new insights into the biology of gut immunity, mechanisms of allograft tolerance, and HIV-associated immune dysregulation, successful outcome is anticipated, particularly in patients who are in need of isolated intestinal and less-organ-contained visceral allografts.

The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

BACKGROUND Fusarium spp. infections have become an emerging and lethal threat to the immunocompromised patient population, especially those with neutropenia. Recently there have been increased reports in solid organ transplant recipients. Presentation is commonly as soft tissue infections several months post-transplant. With high morbidity and mortality, efficacious antifungal therapy is essential. This remains challenging with limited data and no established clinical breakpoints defined. CASE REPORT We report on a modified multi-visceral transplant patient that developed a Fusarium infection only 7 weeks post-transplant in the native hard palate and esophagus, without any soft tissue lesions, which persisted despite aggressive combination treatment with amphotericin B lipid complex and voriconazole. CONCLUSIONS Fusarium spp. infection in solid organ transplant is a significant challenge without clear diagnostic clinical indicators of infection, or specific time of onset, in addition to possible emergence of a more aggressive drug-resistant strain.

Adenovirus enteritis (AE) is uncommon in adult small bowel transplant recipients but can be associated with increased morbidity and mortality.We present 2 cases of AE with contrastingly different outcomes.The first patient was a 49-year-old man with short bowel syndrome (SBS) secondary to multiple surgeries for Crohn disease and initial good evolution.10 months after isolated small bowel transplant, he presented with acute symptoms suspicious of rejection.Small bowel biopsies revealed acute cellular rejection that progressed from mild to severe and was refractory to medical treatment.Ultimately, this led to explantation of the graft and sepsis.The explanted graft revealed features of ongoing acute cellular rejection and superimposed adenovirus inclusions on immunohistochemical stain (LabVision, clone M58+M73, dilution 1:200) and confirmed on electron microscopy.Adenovirus quantitative PCR in blood was negative.Despite intensive therapy, the patient died after 2 months.The second patient was a 40-year-old woman, small bowel transplant recipient secondary to SBS due to endometriosis.Two and half months later, she presented with fever and diarrhea.Small bowel allograft biopsy revealed rare crypt apoptosis, reactive epithelial changes, and intranuclear viral inclusions within epithelial cells, consistent with adenovirus infection.Adenovirus immunostain was initially negative (LabVision).Adenovirus IgG antibody was positive, but confirmatory adenovirus quantitative PCR in blood was negative.Due to the high level of suspicion, the patient was started on Cidofovir 50 mg/kg.Adenovirus immunostain was repeated with a different antibody (Millipore, Clone 2/6 and 20/11, 1:200) and showed numerous positive cells.The symptoms resolved with good outcome.These cases highlight the difficulty of diagnosing AE in adult small bowel recipients considering the low sensitivity of serologic testing and the variability in immunohistochemical stains.AE may coexist with acute cellular rejection, and a high level of suspicion in patients refractory to treatment is essential to improve outcomes.

Background: Patients with iron overload frequently complained of Upper gastrointestinal (GI) symptoms. This study aimed to systemically evaluate the association between hereditary hemochromatosis (HH) and gut inflammation.Patients and Methods: HH patients were identified using the ICD-9 codes. Inclusion criteria were patients with primary HH who had esophagogastroduodenoscopy (EGD) and/or colonoscopy with GI biopsies (N=39). Patients undergoing EGD with duodenal biopsy for the indication of "rule out celiac disease" were included in the control group (N=40). GI biopsy specimens were rereviewed andscored.Results: Of the 39 patients with genetically confirmed primary HH in the study group, 28 (71.8%) had liver biopsy and 25 (89.3%) of them showed iron deposition. Twenty-five patients (64.1%) had EGD and 23 (59.0%) had colonoscopy. Histologic inflammationwas identified in the esophagus in 2 patients (8.0%), stomach in 11(44.0%), duodenum in 2 (8.7%), and colon in 3 (13.0%). Duodenal biopsy specimen was available for rereview in 16 patients (41.0%). Patient demographics were comparable between the 16 cases in the study group and the 40 cases in the control group. On histology, the frequency of intraepithelial lymphocytosis of small intestine was 25.5% in the HH cases versus 2.5% in controls (P=0.020). HH patients also had a greater proportion of intraepithelial neutrophil infiltration (31.2% vs. 2.5%, P=0.006) and lamina propria lymphocyte infiltration (31.2% vs. 0%, P=0.001) than controls.Conclusions: GI inflammation was common in HH patients, which from the different perspective, supports the notion that iron overload may lead to GI inflammation.

The effects of normothermic machine perfusion (NMP) on the postreperfusion hemodynamics and extrahepatic biliary duct histology of donation after cardiac death (DCD) livers after transplantation have not been addressed thoroughly and represent the objective of this study. Ten livers (5 per group) with 60 minutes of warm ischemia were preserved via cold storage (CS) or sanguineous NMP for 10 hours, and then they were reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, the arterial and portal vein flows were stable in the NMP group during the entire reperfusion simulation, whereas they decreased dramatically in the CS group after 16 hours of reperfusion (P < 0.05); these findings were consistent with severe parenchymal injury. Similarly, significant differences existed between the CS and NMP groups with respect to the release of hepatocellular enzymes, the volume of bile produced, and the levels of enzymes released into bile (P < 0.05). According to histology, CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhaging, denudated biliary epithelium, and submucosal bile duct necrosis, whereas NMP livers showed very mild injury to the liver parenchyma and biliary architecture. Most importantly, Ki-67 staining in extrahepatic bile ducts showed biliary epithelial regeneration. In conclusion, our findings advance the knowledge of the postreperfusion events that characterize DCD livers and suggest NMP as a beneficial preservation modality that is able to improve biliary regeneration after a major ischemic event and may prevent the development of ischemic cholangiopathy in the setting of clinical transplantation. Liver Transpl 20:987–999, 2014. © 2014 AASLD.

Introduction. Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers. Materials and Methods. After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology. Results. No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury. Conclusion. Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.